mRNA-Based Anti-TCR CDR3 Tumour Vaccine for T-Cell Lymphoma
Efficient vaccination can be achieved by injections of in vitro transcribed mRNA (ivt mRNA) coding for antigens. This vaccine format is particularly versatile and allows the production of individualised vaccines conferring, T-cell immunity against specific cancer mutations. The CDR3 hypervariable re...
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| Format: | Article |
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MDPI AG
2021-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/7/1040 |
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| author | Marina Tusup Severin Läuchli Natalia Teresa Jarzebska Lars E. French Yun-Tsan Chang Maya Vonow-Eisenring Andreas Su Thomas M. Kündig Emmanuella Guenova Steve Pascolo |
| author_facet | Marina Tusup Severin Läuchli Natalia Teresa Jarzebska Lars E. French Yun-Tsan Chang Maya Vonow-Eisenring Andreas Su Thomas M. Kündig Emmanuella Guenova Steve Pascolo |
| author_sort | Marina Tusup |
| collection | DOAJ |
| description | Efficient vaccination can be achieved by injections of in vitro transcribed mRNA (ivt mRNA) coding for antigens. This vaccine format is particularly versatile and allows the production of individualised vaccines conferring, T-cell immunity against specific cancer mutations. The CDR3 hypervariable regions of immune receptors (T-cell receptor, TCR or B-cell receptor, BCR) in the context of T- or B-cell leukaemia or lymphoma are targetable and specific sequences, similar to cancer mutations. We evaluated the functionality of an mRNA-based vaccine designed to trigger immunity against TCR CDR3 regions in an EL4 T-lymphoma cell line-derived murine in vivo model. Vaccination against the hypervariable TCR regions proved to be a feasible approach and allowed for protection against T-lymphoma, even though immune escape in terms of TCR downregulation paralleled the therapeutic effect. However, analysis of human cutaneous T-cell lymphoma samples indicated that, as is the case in B-lymphomas, the clonotypic receptor may be a driver mutation and is not downregulated upon treatment. Thus, vaccination against TCR CDR3 regions using customised ivt mRNA is a promising immunotherapy method to be explored for the treatment of patients with T-cell lymphomas. |
| first_indexed | 2024-03-10T09:28:21Z |
| format | Article |
| id | doaj.art-740ac46bbfb44586b93eb42bb91c79c1 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T09:28:21Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-740ac46bbfb44586b93eb42bb91c79c12023-11-22T04:41:06ZengMDPI AGPharmaceutics1999-49232021-07-01137104010.3390/pharmaceutics13071040mRNA-Based Anti-TCR CDR3 Tumour Vaccine for T-Cell LymphomaMarina Tusup0Severin Läuchli1Natalia Teresa Jarzebska2Lars E. French3Yun-Tsan Chang4Maya Vonow-Eisenring5Andreas Su6Thomas M. Kündig7Emmanuella Guenova8Steve Pascolo9Department of Dermatology, University Hospital of Zürich, Raemistrasse 100, 8091 Zürich, SwitzerlandDepartment of Dermatology, University Hospital of Zürich, Raemistrasse 100, 8091 Zürich, SwitzerlandDepartment of Dermatology, University Hospital of Zürich, Raemistrasse 100, 8091 Zürich, SwitzerlandDepartment of Dermatology and Allergy, University Hospital, LMU Munich, 80539 Munich, GermanyDepartment of Dermatology, Lausanne University Hospital (CHUV), University of Lausanne, 1000 Lausanne, SwitzerlandDepartment of Immunology, University Hospital of Zürich, Raemistrasse 100, 8091 Zürich, SwitzerlandBioNTech, 55131, Mainz, GermanyDepartment of Dermatology, University Hospital of Zürich, Raemistrasse 100, 8091 Zürich, SwitzerlandDepartment of Dermatology, University Hospital of Zürich, Raemistrasse 100, 8091 Zürich, SwitzerlandDepartment of Dermatology, University Hospital of Zürich, Raemistrasse 100, 8091 Zürich, SwitzerlandEfficient vaccination can be achieved by injections of in vitro transcribed mRNA (ivt mRNA) coding for antigens. This vaccine format is particularly versatile and allows the production of individualised vaccines conferring, T-cell immunity against specific cancer mutations. The CDR3 hypervariable regions of immune receptors (T-cell receptor, TCR or B-cell receptor, BCR) in the context of T- or B-cell leukaemia or lymphoma are targetable and specific sequences, similar to cancer mutations. We evaluated the functionality of an mRNA-based vaccine designed to trigger immunity against TCR CDR3 regions in an EL4 T-lymphoma cell line-derived murine in vivo model. Vaccination against the hypervariable TCR regions proved to be a feasible approach and allowed for protection against T-lymphoma, even though immune escape in terms of TCR downregulation paralleled the therapeutic effect. However, analysis of human cutaneous T-cell lymphoma samples indicated that, as is the case in B-lymphomas, the clonotypic receptor may be a driver mutation and is not downregulated upon treatment. Thus, vaccination against TCR CDR3 regions using customised ivt mRNA is a promising immunotherapy method to be explored for the treatment of patients with T-cell lymphomas.https://www.mdpi.com/1999-4923/13/7/1040in vitro transcribed mRNAivt mRNAvaccineT-cell lymphomaCTCLTCR |
| spellingShingle | Marina Tusup Severin Läuchli Natalia Teresa Jarzebska Lars E. French Yun-Tsan Chang Maya Vonow-Eisenring Andreas Su Thomas M. Kündig Emmanuella Guenova Steve Pascolo mRNA-Based Anti-TCR CDR3 Tumour Vaccine for T-Cell Lymphoma Pharmaceutics in vitro transcribed mRNA ivt mRNA vaccine T-cell lymphoma CTCL TCR |
| title | mRNA-Based Anti-TCR CDR3 Tumour Vaccine for T-Cell Lymphoma |
| title_full | mRNA-Based Anti-TCR CDR3 Tumour Vaccine for T-Cell Lymphoma |
| title_fullStr | mRNA-Based Anti-TCR CDR3 Tumour Vaccine for T-Cell Lymphoma |
| title_full_unstemmed | mRNA-Based Anti-TCR CDR3 Tumour Vaccine for T-Cell Lymphoma |
| title_short | mRNA-Based Anti-TCR CDR3 Tumour Vaccine for T-Cell Lymphoma |
| title_sort | mrna based anti tcr cdr3 tumour vaccine for t cell lymphoma |
| topic | in vitro transcribed mRNA ivt mRNA vaccine T-cell lymphoma CTCL TCR |
| url | https://www.mdpi.com/1999-4923/13/7/1040 |
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